The effect of prophylactic rewarming on postoperative nausea and vomiting among patients undergoing laparoscopic hysterectomy: a prospective randomized clinical study

ABSTRACT BACKGROUND: Postoperative nausea and vomiting (PONV) is a common complication from general anesthesia that impacts on postoperative recovery. OBJECTIVE: To evaluate prophylactic rewarming following general anesthesia, so as to decrease the incidence of PONV among patients undergoing laparoscopic hysterectomy. DESIGN AND SETTING: Prospective randomized clinical study at a hospital in China. METHODS: Sixty-two patients were randomly assigned into two groups. The forced air warming (FAW) group received pre-warmed Ringer's solution with FAW until the end of surgery. The control group received Ringer's solution without FAW. The pre-warmed Ringer's solution was stored in a cabinet set at 40 °C. The FAW tube was placed beside the patient's shoulder with a temperature of 43 °C. RESULTS: Sixty patients completed the study. The FAW group showed significant differences versus the controls regarding temperature. At 6, 24 and 48 hours postoperatively, the incidences of PONV were 53.3%, 6.7% and 3.3% in the FAW group versus 63.3%, 30% and 3.3% in the controls. VAS scores were significantly lower in the FAW group than in the controls at 24 hours (P= 0.035). Forty-item questionnaire total scores in the FAW group were significantly higher than in the controls. The physical independence and pain scores at 24 hours and emotional support and pain scores at 48 hours in the FAW group were higher than in the controls (P < 0.05). There was no difference in hemodynamics or demographics between the two groups (P > 0.05). CONCLUSIONS: Prophylactic rewarming relieved PONV and improved the quality of postoperative recovery. CHINESE CLINICAL TRIAL REGISTER (ChiCTR): ChiCTR-IOR-17012901.


INTRODUCTION
Postoperative nausea and vomiting (PONV) after general anesthesia has high incidence (20%-80%). It is an uncomfortable complication that causes distress for patients. 1 It occurs much more frequently among high-risk patients (60-70%), such as females, individuals who suffer from motion sickness, nonsmokers and individuals with a history of PONV. 2 Laparoscopic surgery is prone to induce postoperative nausea and vomiting, which significantly increases patients' discomfort, such that they hardly take in any nutritious food, which thus results in extending their length of hospital stay. 3 Multiple antiemetic drugs have been applied in clinics, but the efficacy of such treatment comes with risks of adverse events such as excessive sedation, 4 dizziness, dry mouth, dysphoria, mood changes, 5 tachycardia and extrapyramidal signs.
Besides drug therapy, nondrug therapy also provides some help in preventing occurrences of PONV. Intraoperative skin surface rewarming is a common and rapid method that not only can prevent hypothermia but also can improve postoperative comfort. 6,7 Rein et al. 8 and Hamza et al. 9 showed that perioperative temperature protection increased skin blood flow and heat transfer, and also lowered the requirement for analgesics and promoted higher quality of recovery. 10 Reflective blankets, 11 forced-air warmers and warm socks have all been used clinically to prevent shivering and maintain subjective thermal comfort postoperatively, 12 of nausea and vomiting. 4 Some clinical trials have shown that oral administration of warm water for four hours postoperatively had the capacity to significantly decrease the first flatus expulsion, relieve gastrointestinal spasms and help peristalsis return at an early stage of recovery. 14 Therefore, we hypothesized that thermal protection for patients would prevent PONV and provide better benefit in recovery. To test this hypothesis, we applied forced-air warmers combined with warm liquid to maintain temperature fluctuation perioperatively; a 100-mm visual analogue scale (VAS) to evaluate overall postoperative PONV; and a 40-item questionnaire (QoR-40) to measure the quality of recovery.

OBJECTIVE
The aim of this study was to evaluate prophylactic rewarming following general anesthesia, to guard against postoperative nausea and vomiting among patients undergoing laparoscopic hysterectomy.

The present study was registered in the Chinese Clinical Trial
Register with the code ChiCTR-IOR-17012901. This was a prospective randomized study in which 62 patients who were candi- From the surgical list, we identified the patients who were eligible to become involved in the clinical trial. Patients who conformed to the inclusion criteria were allocated before the surgery either to the forced air warming (FAW) group or to the control group by means of numbers in identical sealed envelopes, according to a random number table that was created through a computer by an independent statistician. One of the anesthesiologists (WLL) made an evaluation and recorded the data after the participants had signed the consent form.
An independent nurse who was not involved in caring for these patients opened the envelopes before the operation and prepared the fluids and FAW. The FAW tube was placed beside the patient's shoulder with the temperature at 43 °C. Two of the anesthesiologists (LDD, SYL), who were unaware of the allocation group, performed the general anesthesia and all intraoperative data recording, and another investigator (WLL) was in charge of all postoperative assessments, while blinded to the group identity.

Subjects
The inclusion criteria were that the subjects needed to present the following: American Society of Anesthesiologists (ASA) physical status I/II; aged 20 to 60 years; consent to their participation in the study until the end; scheduled to undergo laparoscopic hysterectomy. Written informed consent was obtained from all subjects. All of them answered the QoR-40 questionnaire independently.
Presentation of any of the following were deemed to be exclusion criteria: allergy; bronchial asthma; coronary heart disease; obesity-related diabetes mellitus; hypertension; BMI > 30 kg/m 2 ; cardiac, hepatic or renal dysfunction; psychiatric disease; chronic pain; fever; history of alcohol or opioid abuse; intake of any nonsteroidal analgesics or antiepileptic drugs within 48 hours before surgery; or history of gastrointestinal disease (peptic ulcer, Crohn's disease or ulcerative colitis). Patients were withdrawn from the groups if their laparoscopy was converted to open surgery.
Sixty female patients aged 20 to 60 years who presented ASA physical status I or II and had been scheduled for primary gynecological laparoscopic surgery were randomly assigned to two groups. Patients in the FAW group received pre-warmed Ringer's solution that was stored in a heating cabinet set at 40 °C and was applied with forced air warming (FAW) that was switched on until the end of surgery. Patients in the control group received normal general anesthesia with normal Ringer's solution, i.e. FAW was switched off. To ensure that the surgery went smoothly, we set the patients' intraoperative temperature to be not lower than 35 °C.
In the event of lower temperatures occurring in the control group, our intention was to stop the trial and take protective measures.
Anesthesia was induced in all patients by means of propofol 2 (mg/kg) and sufentanil (0.3-0.5 μg/kg), and intubation was done using cisatracurium (2 mg/kg). Anesthesia was maintained by means of sevoflurane, propofol and remifentanil. The bispectral index (BIS) was monitored to maintain it at 45-55 in order to control the infusion speed of anesthetic drugs.
Mechanical ventilation was performed to maintain PetCO 2 at 35-40 mmHg. Sufentanil (0.1 mg/kg per 30 minutes) was administered during the surgery to provide analgesia. Intravenous ondansetron (8 mg) was administered to prevent postoperative nausea and vomiting. When patients presented spontaneous breathing, consciousness was recovered by using neostigmine and atropine, and then the tracheal tube was extracted.

Data analysis and statistics
The demographic profiles were analyzed by means of the independent-sample t test. The paired-sample t test was used to test for significant differences in ∆T between the two groups.
The Wilcoxon test with the Mann-Whitney U test was used to analyze PONV scores and QoR-40 scores. Repeatedmeasurement analysis of variance (ANOVA) followed by the Huynh-Feld correction was used for analysis on MAP and heart rate. Occurrences of shivering were tested using the chi-square test with Fisher's exact test.
All values were presented as means ± standard deviation (SD).
All the analyses were performed using the SPSS statistical software (SPSS Inc., Chicago, Illinois, USA). P-values < 0.05 were considered statistically significant.

Postoperative nausea and vomiting:
At 6 hours after the operation, the incidences of PONV were 53.3% (16/30) in the FAW group and 63.3% (19/30) in the control group, within which the vomiting rates were 20% (6/30) in the FAW group and 23.3% (7/30) in the control group.
However, there was no statistically significant in VAS scores (P = 0.258). At 24 hours after the operation, the incidences of PONV were 6.7% (2/30) in the FAW group and 30% (9/30) in the control group, within which the vomiting rates in the two groups were equal, at 3.3% (1/30). The VAS scores in the control group were significantly higher than those in the FAW group  0.3833 ± 0.24507; P = 0.000; Figure 1).

Results from QoR-40:
All the patients (n = 30 in each group) received the QoR-40 questionnaire at three times: before the operation (T0), 24 hours after the operation (T1) and 48 hours after the operation (T2).
At T1, the patients in the control group had lower overall QoR-40 scores than the patients in the FAW group (P = 0.027) and lower scores for the PI and P dimensions (P = 0.032, P = 0.034 respectively). At T2, the overall QoR-40 scores in the two groups were higher and returning towards the preoperative level. Patients in the FAW group showed better recovery than those in the control group, with a statistically significant difference (P = 0.006). The ES and P dimensions in the control group had lower scores than those of the T group (P = 0.024 and P = 0.002, respectively; Table 2).    Figure 2). Both MAP and heart rate values decreased at the time of tracheal cannulation and then maintained a lower level than the baseline. However, these values tended to remain within an acceptable range once surgery had commenced.

Occurrence of shivering:
Occurrences of shivering were associated with high incidence of low temperature, compared with the control group (P = 0.024; Table 3).

Patient characteristics:
Sixty-two patients who were candidates for laparoscopic hysterectomy under general anesthesia were enrolled for this study. Two patients were excluded as a result of factors such as changes to the surgical procedure and blood sample loss.  Table 4).

DISCUSSION
PONV is a commonly encountered symptom among patients in a variety of clinical settings. 18 PONV causes distress for patients and affects postoperative recovery quality, although the precise mechanism is still unclear. The main finding in our study was that prophylactic rewarming (pre-warmed Ringer's solution with FAW) could effectively ameliorate the condition of PONV at 24 hours after the operation. It also helped to improve the quality of early recovery among these laparoscopic hysterectomy patients, 24 hours and 48 hours after the operation.
Perioperative hypothermia has been found to tend to induce occurrence of nausea and vomiting, in many studies. [19][20][21] In our study, temperature values in both groups decreased markedly after intubation. However, the degree of temperature decline in the FAW group was reduced, compared with the control group, from the time of 30 minutes after intubation to the time of 90 minutes after intubation. The results suggested that pre-warming fluids applied in association with FAW were able to provide steady  Values are expressed as means ± standard deviation (SD). X axis encompasses the baseline intubation and 10 minutes, 20 minutes, 30 minutes, 40 minutes, 50 minutes and 60 minutes after induction of anesthesia. There were no significant differences between the two groups.

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heat transfer throughout the surgical procedure and minimized the core temperature loss, which was caused mostly by surgical and anesthesia factors.
It is hard to maintain normothermia at a typical operating room temperature. Some studies have reported that general anesthesia has the capacity to reduce metabolic heat production by about 30%. However, perioperative warming devices may compensate for this. 22 In our study, hypothermia possibly caused occurrences of PONV, notably at 24 hours after the operation (the rate of occurrence of nausea and vomiting was 6.7% in the FAW group versus 30% in the control group). VAS scores at 24 hours in the FAW group were much lower than those in the control group. This suggested that the patients in the FAW group were in a better physical condition at 24 hours after the operation, with low occurrence of PONV. However, the use of antiemetic drugs in the ward in the two groups was 46.7% in the FAW group and 56.7% in the control group.
Some studies have shown that occurrences of nausea are more resistant to interventions. 23 The data from the ward suggested to us that clinicians in the ward were possibly prescribing antiemetic drugs as prophylaxis for PONV. Quigley et al. stated that most clinically encountered episodes of PONV were typically short-lived and self-limited. 24 Because of the prophylactic antiemetic drugs, the number of times that patients in the FAW group asked for relief from nausea diminished.
In addition, we observed that frequency of occurrence of postoperative shivering increased in the control group. Along with PONV, shivering caused discomfort for the patients recovering from general anesthesia, even though none of them presented temperatures under 35 °C. This possibly implied that pre-warming decreased the risk of surgical complications. Patients were able to absorb nutrients earlier, which was conducive to recovery. 25 Furthermore, the QoR-40 scores suggested that the higher these were, the faster and better the quality of recovery were. The FAW group showed better status for physical independence (PI) and pain (P) than the control group at 24 hours after the operation.
Meanwhile, presence of pain itself increased the occurrences of PONV. Moreover, postoperative opioid administration likewise has been found to give rise to a high risk of PONV. 26 At 48 hours after the operation, the ES scores in the FAW group were clearly higher than those in the control group.
Most patients in both groups lay in a semi-reclining position on the bed. Better body condition and peaceful psychological status would be expected to accelerate rehabilitation. However, we found that for some patients whose psychological status was poor at the outset, their condition could not be improved through surgery because their pessimism affected the functioning of their immune system. [27][28][29] Some studies have demonstrated that the medial prefrontal cortex and the pregenual anterior cingulate cortex are involved in people's cognitive and emotion functioning. Vitaly Napadow showed that the presence of stress, emotion and fear conditioning was associated with increasing sensation of nausea in the brain through functional magnetic resonance imaging (fMRI). 30 Some research has suggested that knowledge of the risk factors for nausea and vomiting, along with knowledge of health and affective factors, would lead to healthier behavior. 31,32 At 24 hours and 48 hours after the operation, the total QoR-40 scores in the FAW group were significantly higher than those in the control group. The quality of recovery in the FAW group suggested that patients with pre-warming were not undergoing any intensely physiological stress reactions, such as PONV, shivering and heat loss.
There were some limitations to this study. Firstly, we did not test any serum biochemical parameters to reflect the patients' inner reactions to nausea and vomiting through maintenance of normal temperature. Secondly, we did not test the PONV intensity scale, which could have provided supplementary data to explain the relationship between prophylactic rewarming and PONV.

CONCLUSIONS
Prophylactic rewarming effectively relieved the condition of PONV and provided some help in improving the quality of postoperative recovery among these patients undergoing laparoscopic hysterectomy.